Alcohols, C16-18

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Alcohols, C16-18 is a member and is from Long Chain Alcohols (C6-22 primary aliphatic alcohols) category.
The Long Chain Alcohols (C6-22 primary aliphatic alcohols) category is considered suitable as a source of data for Alcohols, C16-18.
Considered valid for read-across for purposes of classification.
No further vertebrate testing can be justified.

Long Chain Alcohols (C6-22 primary aliphatic alcohols) category covers a family of 30 primary aliphatic alcohols within a carbon chain length range of C6-C22. Commercial products generally include several aliphatic alcohol components, with a range of carbon chain lengths present. The family consists of alcohols with varying compositions and structures. Composition depends on the route to manufacture and the related feedstocks. Most of the alcohols have linear carbon chains but certain manufacturing processes create branched structures. Data are also available for eleven other similar substances, which support the category. Non-sponsored alcohols may not be HPV or may not be produced by members of the consortium, but have structures similar to sponsored linear alcohols.

Key points are that the members share:
• The same structural features
• Similar metabolic pathways
• Common mode of ecotoxicological action
• Common levels and mode of human health related effects

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2022

Reference 2

Reference Type:

publication

Title:

Percutaneous absorption of aliphatic compounds.

Author:

Iwata Y, Moriya Y, Kobayashi T

Year:

1987

Bibliographic source:

Cosmet. Toiletries 102(2): 53-68

Materials and methods

Objective of study:

absorption

distribution

excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: Groups of 3 hairless mice were used. The 1-C14 labelled test substances were applied to the dorsal skin using a plaster for a 24 hour period. Immediately following application of the test material each animal was placed in a container to measure expiratory excretion. At the end of the exposure period the treated area of skin was excised and dissolved using tissue solubiliser. The carcass was homogenised in a blender wwith sodium hydroxide. An aliquot of the homogenate was then dried and combusted for determination of radioactivity.
The effect of different solvents and concentration of the solvent was also investigated. The role of skin irritation in absorption of test substance was also examined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecan-1-ol

EC Number:

253-149-0

EC Name:

Hexadecan-1-ol

Cas Number:

36653-82-4

Molecular formula:

C16H34O

IUPAC Name:

hexadecan-1-ol

Details on test material:

n-octyl alcohol; n-decyl alcohol, lauryl alcohol and cetyl alcohol all radiolabelled (1-C14) and >98% pure.

Radiolabelling:

yes

Test animals

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Groups of 3 hairless mice were used. The 1-C14 labelled test substances were applied to the dorsal skin using a plaster for a 24 hour period. Immediately following application of the test material each animal was placed in a container to measure expiratory excretion. At the end of the exposure period the treated area of skin was excised and dissolved using tissue solubiliser. The carcass was homogenised in a blender wwith sodium hydroxide. An aliquot of the homogenate was then dried and combusted for determination of radioactivity.

Administration / exposure

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

24 hour period.

No. of animals per sex per dose / concentration:

Groups of 3 hairless mice were used

Control animals:

yes

Results and discussion

Any other information on results incl. tables

Distribution results were reported for lauryl alcohol (98% pure). 95% of the dose adminstered was recovered from the application site at 24 hours after dosing. 0.13% remained in the body while 0.10% was excreted in the urine and faeces. 2.61% was excreted in expired air as CO2. The ratio of the amount of compound excreted via expired air to the amount absorbed is the expiratory excretion rat. It was 91% for lauryl alcohol. The respiratory excretion rates for all the other alcohols investigated were >65% although all the actual data is not reported.

Absorption decreased with increasing carbon chain length. The absorption rate was investigated in different solvents (squalene, castor oil, triethyl citrate (TEC). The percutaneous absorption rate of undiluted n-octanol was 50%, this was increased in squalene but decreased in castor oil or TEC. This was also reported with the other alcohols tested and the tendency was more pronounced at higher concentrations.

The degree of skin irritation was proportionally related to the degree of percutaneous absorption.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
Following skin application of lauryl alcohol about 2.84 % of the administered dose was absorbed. Of this absorbed dose >90% was excreted in expired air (CO2). A similar trend was observed with the other alcohols tested. Absorption decreased with increasing carbon chain length and was affected by solvent and concentration.

Executive summary:

At least 65% of the absorbed dose is excreted as CO2 in the expired air. Absorption decreased with increasing carbon chain length and was affected by solvent and concentration.